The Incidence And Mechanism Of Gastrointestinal Cancer-associated Anemia And Clinical Study Of Iron Intervention

【Background】The definition of cancer related anemia is decrease of red blood cells or hemoglobin is low which is caused by cancer or chemotherapy. The incidence of cancer-related anemia is high which could cut down the quality of life and affect tumor recurrence,prognosis and effect of chemotherapy.Malignant tumos of digestive system are common,There is lack of reports including bulk cases. The treatment of cancer-related anemia blood is covered by transfusions and EPO and many studies have shown that intravenous iron has a fast and efficientive function for iron deficiency anemia treatment and could reduce EPO resistance reduce cancer-related anemia in some cases. Intravenous iron alone is proven to be having good results in chronic kidney disease and postpartum anemia, but its role in gastrointestinal cancer with anemia is not clear. Tumor-associated anemia is a chronic disease, anemia, chronic in vitro found thatanemia may be associated with inflammatory diseasestatus and hepcidin related, but less study on vivo aspects.【Objective】Firstly,to find out the incidence of the cancer related anemia caused by nine kind common digestive cancer and analyze the correlative factors of tumor related anemia occurred in colorectal cancer and determine the prevalence of cancer-related anemia and iron deficiency anemia (IDA) in gastric cancer and colorectal cancer patients. Secondly,to descripte the safety, effectiveness and efficacy differences of dirrerent formation of iron including intravenous iron and oral iron in improving anemia in gastrointestinal tumor surgery and the effectiveness and security of preoperative intravenous iron alone in patients of gastrointestinal cancer with anemia. The third Objectives is to investigate the expression of hepcidin in gastric cancer, colorectal cancer and normal intestinal epithelium. To find out he relationship among inflammatory factors and hepcidin, anemia, and clinical pathological characteristics in Stomach and colorectal cancer patients. PartⅠthe Investigation of the Incidence and Related Factors of Cancer-Related Anemia in Digestive System Cancer and Stomach and Colorectal before and after Surgery【Methods】To collecte the inpatients information admitted in Beijing Union Medical College Hospital from 2000 to 2009 that were diagnosed as one of cancer below esophageal carcinoma,carcinoma of gastric cardia and gastric,carcinoma of duodenum,carcinoma of small intestine,hepatocellular carcinoma,cholangiocarcinoma,cancer of pancreas,colon carcinoma and carcinoma of rectum.We excluded the patients with haemocytolysis or hepatonephric dysfunction and analysed the cancer related anemia among the nine cancer.319 colorectal cancer patients of 10218 cases entered the study of analyzing the risk factors of cancer related anemia. A cross-sectional study was designed to investigate the incidence of cancer related anemia and iron deficiency anemia in Beijing eight general hospitals from August 2009 to December 2009.【Results】10218 gastrointestinal cancer patients entered and the range of average age of onset of gastrointestinal cancer was 50.72 to 62.36 yrs. According to the China standards of anemia, the highest incidence of anemia were in duodenal cancer and small bowel cancer in all digestive system cancer, respectively 60.45% and 64.71%.The incidence of anemia in Gastric cancer and colon cancer was 36.63% and 42.60% and 20.38% rectal cancer patients immerged anemia, which was lower than the former two. The radical operation was most popular in colon carcinoma and rectal carcinoma 81.80% and 81.13% respectively and the rate of tumor resection was least in hepatocellular carcinoma and pancreatic carcinoma (42.97% and 38.41%). The incidence of anemia was different among different digestive system cancers. Most of the anemia was slight and the critical anemia was easily observed in colon carcinoma. In most gastrointestinal cancer,the average age of patients with anemia was older than which with no anemia. Gender distribution was significantly different in Small intestine, hepatocellular carcinoma, cholangiocarcinoma, pancreatic cancer and rectal cancer anemia. In 319 cases,141 (44.20%) had anemia. The incidence of anemia was 62.20% in Right hemicolon cancers patients (including caecum cancer), while the incidence of anemia was 23.82% in rectal cancer; it was 36.23% in the rest colorectal cancer. Cardia insufficiency, melena, tumor location, T staging, Hypoproteinemia were related to anemia. Anemia and hypoproteinemia were risk factors for perioperative blood transfusion, The OR of which was 3.004,8.356 respectively.131 gastric cancer patients and 131 colorectal cancer patients were enrolled.The preoperative morbidity of Cancer-related anemia was 36.6% in gastric cancer and 37.4% in colorectal cancer, but the postoperative morbidity increased to respectively. IDA was the primary cause of Cancer-related anemia not just pre-operation but after surgery. Age and tumor in the right colon were risk factors of anemia in gastrointestinal tumors patients. Only 10% anemia patients were offered chalybeate therapy, more than 50% patient accepted blood transfusion.PARTⅡThe High Expression of Hepcidin and its Association with Inflammatory Factors in Serum in Stomach and Colorectal Cancer[Methods] Consecutively collecting the clinical data and pathological data of 101 cases which were hospitalized in Beijing Union Medical College Hospital from August 2010 to March 2011. Venous serum of 12 cases of normal healthy people and the 77 cases was collected in the early morning the next day after admission.Elisa was used to detecte IL-1β, IL-6, IL-12, TNf-α, hepcidin, CRP, Hs-CRP. The expression of hepcidin in tumor and normal Tissue was detected by immunohistochemistry in 62 patients of 77 cases.【Results】Hepcidin expression in stomach and colorectal cancer was high,but low in normal tissue of the gastrointestinal tract.and clinical pathological features and of anemia among cancer patients is not associated with hepcidin expression.Compared size and the diameter of tumor ulcers, P values were <0.05. with healthy control subjects, IL-1β, IL-6, IL-12, TNf-α, hepcidin, CRP, Hs-CRP level in cancer patients peripheral blood is high (P<0.05). There was no dirrerence in expression level of inflammatory factors between gastric cancer and colorectal cancer patients (P>0.05). In cancer patients with anaemia, IL-1β, IL-6, IL-12, TNf-α, hepcidin, CRP, Hs-CRP levels were higher than those without anemia patients, but no statistically significant difference appear in hepcidin level(P=0.059).The mean of CRP and Hepcidin respectively were different within different tumor T stage, which hepcidin is higher in Tis～2 than that in T3～4 (P=0.026). Compared with no lymph node metastasis, IL-12 leval in patients with lymph node metastasis was significantly different (P=0.009). among various inflammatory factors, IL-6 had the correlation with hemoglobin and (r =-0.262, P<0.05), Hs-CRP had the correlation with tumorPartⅢStudy on Iron Supplement to Gastrointestinal Tumor Anemia before or after Surgery【Methods】A RCT study on effectiveness of different iron on anemia pre and after surgery was taken out in beijing Union Medical College Hospital from Junuary 2010 to junuary 2011 in gastrointestinal cancer patients.Patients with iron deficiency anemia were administrated of intravenous iron by the way of intravenous drip and the efficacy was assessed about 14 days after the treatment. Perioperative blood transfusion dose of those subjects was compared with that of the same period of hospitalization in patients with anemia.【Results】Among control group, oral iron group and intravenous iron group, hemoglobin and red blood cell count of the intravenous iron group after 2 weeks addiministration increased significantly with the remaining significant difference compared with the rest two groups. Compared with the control group, hemoglobin and red blood cell count of oral iron group were higher. Serum iron level after intravenous iron infusion preserved at a higher level, with the gradual return to normal level after 12 weeks, are statistically significant with the other two groups during observation period. A total of 31 patients entered and completed the study, in which 5 of small intestinal stromal tumors,10 cases of gastric cancer and 16 cases of colorectal cancer.The iron traetment was determited effective in 5 cases of gastric cancer,and 11 patients in 16 colorectal cancer patients. Application of preoperative intravenous iron improved hemoglobin level rapidly (85.16±15.05 VS 96.45±9.73),and also increased red blood cell count (3.32±0.69 VS 4.04±0.36). MCV, MCHC and MCH which are indicators of red blood cell were improved after treatment. Shortly after intravenous iron treatment,serum iron and serum ferritin levels were significantly increased compared with that before treatment. And the patients with a hemoglobin levels before treatment<100g/L had a better response to intravenous iron compared to which with pre-treatment hemoglobin level≥100g/L. Some patients of gastric cancer were poor to respouse to intravenous iron,but there was no no significant difference between the gastric cancer and colorectal cancerpatients.3 cases of gastric cancer with poor response to the iron received adjuvant therapy, who has a clear increase in hemoglobin levels at 3 weeks after the iron treatment. iron treatment can reduce the perioperative transfusion of red blood cell dose compared with the non treatment anemia patients with cancer.【Conclusion】1. The age liability of gastrointestinal caner is 50 yrs to 70yrs. The proportion of radical surgery is high for colorectal cancers but is low for hepatocellular carcinoma and pancreatic carcinoma. The duodenum carcinoma and carcinoma of small intestine are most adapted to anemia, following by colon carcinoma and cholangiocarcinoma, but the lowest is esophageal carcinoma. Anemia is more common in elder patients. Anemia in Small intestine, hepatocellular carcinoma, cholangiocarcinoma, pancreatic cancer and rectal cancer may be related with gender.The occurrence of anemia in colorectal cancer has no significant correlation with clinical stage. Cardiac insufficiency, melina, tumor location, staging and hypoproteinemia might be considered as risk factors of anemia in colorectal cancer. The patient with anemia or hypoproteinemia is more possible to accept perioperative blood transfusion.Cancer-related anemia is a common clinical manifestation of patients with gastrointestinal tumors; the most common cause is IDA. And Cancer-related anemia occurred more frequently in elder, patients with right colon tumor. The treatment to Cancer-related anemia is insufficient A Systematic and normative therapy to Cancer-related anemia is needed to be established.2. The oral iron and intravenous iron can also improve anemia in gastrointestinal cancer patients. compared with oral iron, intravenous iron has rare complications, rapid rise in hemoglobin and fast supplement iron store.In the gastrointestinal cancer patients with pre-treatment anemia, intravenous iron alone can increase the hemobolin of preoperative anemia patients, decrease the iron deficiency of the orgianism safely and rapidly, and can reduce perioperative blood transfusion.the efficacy of intravenous iron may be affected by the degree of anemia. Intravenous iron on anemia caused by different tumor efficacy may be different. neoadjuvant chemotherapy can promote the efficacy of iron sucrose in patients with poor effectness.3. Hepcidin is highly expressed in gastrointestinal cancer and may be involved in tumorigenesis. Cancer patients have chronic inflammation. Chronic inflammation participates the tumor progression and the formation of tumor anemia. Hs-CRP is expected to be predictors of tumor burden.